Pericyclic — orthoester [3,3]-shift
Johnson-Claisen rearrangement
How the Johnson-Claisen rearrangement works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Allylic alcohol, MeC(OEt)₃, cat. EtCO₂H. Conditions: Toluene or neat, 110–140 °C (EtOH removed). Bonds formed: C–C (new σ); C=O (ester); bonds broken: C–O (allylic); π C=C. Stereochemistry: Chair TS; chirality transfer; usually E-alkene control. Rate and selectivity: [3,3] step rate-limiting; acid speeds exchange.
At a glance
Step 1: Mixed orthoester forms
An allylic alcohol reacts with a trialkyl orthoacetate under mild acid, exchanging one alkoxy group for the allylic oxygen and forming a mixed orthoester intermediate.
Step 2: Ketene acetal by loss of EtOH
Loss of one equivalent of alcohol from this orthoester generates a vinyl ether-ketene-acetal-like species — a new C=C bond conjugated with the remaining alkoxy groups, positioned exactly like the vinyl ether half of an ordinary Claisen substrate.
Step 3: [3,3]-Sigmatropic shift
Heating drives the same [3,3]-sigmatropic shift used throughout this rearrangement family, delivering a γ,δ-unsaturated ester directly — this variant reaches an ester product straight from an allylic alcohol, without needing the strong-base enolate-trapping step the Ireland-Claisen rearrangement requires.
Abbreviations and terms
- OEt
- Ethoxy. –OCH₂CH₃.
- EtOH
- Ethanol. Polar protic solvent.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Johnson-Claisen rearrangement | 2-Aza-Cope rearrangement | Eschenmoser-Claisen rearrangement | |
|---|---|---|---|
| Reagents | Allylic alcohol, MeC(OEt)₃, cat. EtCO₂H | Homoallylic amine, aldehyde (to give the iminium), acid | Allylic alcohol, Me₂NC(OMe)₂CH₃ (DMA-DMA) |
| Conditions | Toluene or neat, 110–140 °C (EtOH removed) | Mild heat or RT (cationic variant), CH₂Cl₂ or MeCN | Xylene or toluene, 110–160 °C (MeOH removed) |
| Stereochemistry | Chair TS; chirality transfer; usually E-alkene control | Chair TS; stereo transferred | Chair TS; chirality transfer from the carbinol |
| Rate / selectivity | [3,3] step rate-limiting; acid speeds exchange | Faster than all-carbon Cope (cationic N) | [3,3] step rate-limiting; no acid or base needed |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Johnson-Claisen rearrangement?
Allylic alcohol, MeC(OEt)₃, cat. EtCO₂H. Conditions: Toluene or neat, 110–140 °C (EtOH removed).
Which bonds are formed and which are broken?
Formed: C–C (new σ); C=O (ester). Broken: C–O (allylic); π C=C.
What is the stereochemical outcome?
Chair TS; chirality transfer; usually E-alkene control
What controls the rate or the selectivity?
[3,3] step rate-limiting; acid speeds exchange
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti